Placental Growth Factor Influences Maternal Cardiovascular Adaptation to Pregnancy in Mice1

Abstract

In healthy human pregnancies, placental growth factor (PGF) concentrations rise in maternal plasma during early gestation, peak over Weeks 26-30, then decline. Because PGF in nongravid subjects participates in protection against and recovery from cardiac pathologies, we asked if PGF contributes to pregnancy-induced maternal cardiovascular adaptations. Cardiovascular function and structure were evaluated in virgin, pregnant, and postpartum C56BL/6-Pgf(-) (/) (-) (Pgf(-) (/) (-)) and C57BL/6-Pgf(+/+) (B6) mice using plethysmography, ultrasound, quantitative PCR, and cardiac and renal histology. Pgf(-/-) females had higher systolic blood pressure in early and late pregnancy but an extended, abnormal midpregnancy interval of depressed systolic pressure. Pgf(-/-) cardiac output was lower than gestation day (gd)-matched B6 after midpregnancy. While Pgf(-) (/) (-) left ventricular mass was greater than B6, only B6 showed the expected gestational gain in left ventricular mass. Expression of vasoactive genes in the left ventricle differed at gd8 with elevated Nos expression in Pgf(-) (/) (-) but not at gd14. By gd16, Pgf(-) (/) (-) kidneys were hypertrophic and had glomerular pathology. This study documents for the first time that PGF is associated with the systemic maternal cardiovascular adaptations to pregnancy.

Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice

“…Therefore, we compared the litter sizes, resorption rates, and embryonic weights and found no significant differences between KO and WT mice ( Figure 2, C-E). These findings are in concordance with the previously reported normal fertility and litter size of PlGF KO mice (16,23). The embryo/placenta ratio was significantly decreased in PlGF KO compared with WT ( Figure 2G) due to increased placental weight in PlGF KO mice ( Figure 2F and Supplemental Table 1).…”

“…PlGF is upregulated in pregnancy, with levels peaking in the serum of pregnant women in the early third trimester (10,21,22). In pregnant mice, PlGF has been shown to influence maternal cardiovascular physiology (23). In the placenta, it is expressed in trophoblast giant cells and decidual natural killer cells (21,24).…”

Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice

“…For example, interleukin 15 is tightly regulated 82 and important for vascular remodeling at the maternal fetal interface 83 for CD8 T-cell homeostasis 84,85 and for tissue-resident T-cell development. 86 Based on these findings herein, and others, 37,50 we speculate that unique interaction between immune and vascular systems is set by the experience of pregnancy and placenta-related factors 87 and continues in PP. This in turn influences subsequent susceptibility to cardiovascular stress.…”

Cardiac output and related haemodynamics during pregnancy: a series of meta-analyses

“…While this finding has not been observed previously in the literature, the consistent CIs in these meta-analyses suggest that this is a physiological phenomenon. Speculatively, this decline may be due to the result of changes in LV wall stress37 and/or reductions in hormonal concentrations in late third trimester, such as placental growth factor,38 but future investigations are warranted.…”